Objective To predict the effect of paeoniflorol on neurological function recovery and neuroinflammation after traumatic brain injury(TBI)and evaluate its potential value in clinical practice.Methods A model of TBI in adult mice was established by controlled cortical impingement(CCI)method,and the therapeutic efficacy of paeoniflorol was evaluated after tail vein injection.Network pharmacology predicted that p38 MAPK/NF-κB was a potential route for the treatment of TBI with paeoniflorol.Western blotting and enzyme-linked immunosorbent assay were used to evaluate the expression of target proteins and inflammatory cytokines.Nissl staining was used to observe neuronal damage.Modified Neurological Severity Score(mNSS)was used to evaluate neurological recovery after TBI.Results Paeoniflorol administration after TBI prevented neuronal death,reduced neuroinflammation and promoted neurological recovery in CCI mice.Network pharmacology studies had shown that paeoniflorol may reflect its therapeutic efficacy through the p38 MAPK/NF-κB pathway.Conclusions Paeoniflorol has superior neuroprotective and anti-inflammatory properties during the course of TBI disease development,and its mechanism may be related to the regulation of the p38 MAPK/NF-κB signaling pathway.